微塑料和纳米塑料已成为无处不在的环境污染物。这些塑料对人类健康构成的威胁推动了对其病理生理学和毒理学的研究,但人们对它们的许多基本特性(例如体内药代动力学)仍然知之甚少。在这项研究中,我们利用正电子发射断层扫描 (PET) 来追踪通过气管内和静脉注射给小鼠的微塑料和纳米塑料的体内命运。为此,用含异硫氰酸盐的去铁胺 (DFO) 变体修饰 1 μm 和 20 nm 直径的胺官能化聚苯乙烯颗粒,并用正电子发射放射性金属 [89Zr]Zr4+ 进行放射性标记。两种放射性塑料——[89Zr]Zr-DFO-PS1000 和 [89Zr]Zr-DFO-PS20——都以大约 95% 的放射化学产率生产,并在 37 °C 下发现在人血清和模拟肺液中,在一周内对脱金属保持 >85% 的稳定性。[89Zr]Zr-DFO-PS1000 和 [89Zr]Zr-DFO-PS20 与 MH-S 细胞的孵育显示,前者的大部分在 4 小时内被肺泡巨噬细胞吞噬,而后者在很大程度上逃避了消耗。最后,在小鼠静脉内和气管内给药时询问放射性塑料的体内行为。PET 成像和生物分布实验显示,静脉注射的塑料主要在肝脏和脾脏中积累,注射后 168 h 肝脏放射性浓度分别为 101 ± 48 %ID/g 和 92 ± 22 %ID/g[89Zr]Zr-DFO-PS1000 和 [89Zr]Zr-DFO-PS20。 相比之下,通过气管内安装接受放射性塑料的小鼠在一周结束时在肺部的摄取率最高:[89Zr]Zr-DFO-PS1000 为 4 ± 2 %ID/g,[89Zr]Zr-DFO-PS20 为 32 ± 6 %ID/g。最终,这项工作说明了暴露途径在塑料颗粒的生物积累中起的关键作用,揭示了大小会极大地影响吸入颗粒的肺滞留,并强调了 PET 成像作为研究环境污染物药代动力学工具的价值。
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Unraveling the in vivo fate of inhaled micro- and nanoplastics with PET imaging
Microplastics and nanoplastics have become ubiquitous environmental pollutants. The threat these plastics pose to human health has fueled research focused on their pathophysiology and toxicology, yet many of their fundamental properties — for example, their in vivo pharmacokinetics — remain poorly understood. In this investigation, we have harnessed positron emission tomography (PET) to track the in vivo fate of micro- and nanoplastics administered to mice intratracheally and intravenously. To this end, 1 μm and 20 nm diameter amine-functionalized polystyrene particles were modified with an isothiocyanate-bearing variant of desferrioxamine (DFO) and radiolabeled with the positron-emitting radiometal [89Zr]Zr4+. Both radioplastics — [89Zr]Zr-DFO-PS1000 and [89Zr]Zr-DFO-PS20 — were produced in ∼95% radiochemical yield and found to be >85% stable to demetallation over one week at 37 °C in human serum and simulated lung fluid. The incubation of [89Zr]Zr-DFO-PS1000 and [89Zr]Zr-DFO-PS20 with MH-S cells revealed that the majority of the former were phagocytosed by alveolar macrophages within 4 h, while the latter largely evaded consumption. Finally, the in vivo behavior of the radioplastics was interrogated in mice upon intravenous and intratracheal administration. PET imaging and biodistribution experiments revealed that the intravenously injected plastics accumulated primarily in the liver and spleen, yielding hepatic radioactivity concentrations of 101 ± 48 %ID/g and 92 ± 22 %ID/g at 168 h post-injection for [89Zr]Zr-DFO-PS1000 and [89Zr]Zr-DFO-PS20, respectively. In contrast, the mice that received the radioplastics via intratracheal installation displayed the highest uptake in the lungs at the end of one week: 4 ± 2 %ID/g for [89Zr]Zr-DFO-PS1000 and 32 ± 6 %ID/g for [89Zr]Zr-DFO-PS20. Ultimately, this work illustrates the critical role that the route of exposure plays in the bioaccumulation of plastic particles, reveals that size dramatically influences the pulmonary retention of inhaled particles, and underscores the value of PET imaging as a tool for studying the pharmacokinetics of environmental pollutants.